Week 5 - G - Renal transplantation Flashcards
What is the treatment of choice for end stage renal failure?
This would be a renal transplant
What is the classification of end stage renal failure?
GFR<15 or patient on renal replacement therapy
When was the first renal transplant?
In 1954 between monozygotic twins - The Herrick twins
The blood types and the HLA (human leuocyte antigen) need to match in order for a successful transplant What are the four blood groups? Which can donate to all blood groups but can only recieve blood from others with the same blood type?
O, A, B, AB O - can give to any blood group but can only receive blood form itself
HLA are cell surface proteins expressed on cells. These activate the immune system if non self and cause rejection What are the three main important HLA in transplant?
HLA A HLA B HLA DR
Why are HLA so important in their role in transplant?
If patients have preformed antibodies against their graft, this may lead to graft rejection Matching HLA improves the chances of transplant survival
Which type of Tcell promotes the formation of B cells to produce antibodies against the graft?
CD4 Tcells
What are the three main types of host transplant rejection? What is the time period for each time of rejection to occur?
Hyperacute rejection (minutes to hours) Acute graft failure ( 6 months)
What happens in hyperacute hypersensitivity?
due to pre-existing antibodies against ABO or HLA antigens
What happens in acute hypersensitivity? How is it treated?
Acute usually happens within 6 months due to mismatched HLA. Cell-mediated (cytotoxic T cells) Treat with methylprednisolone and increase immunosuppresion
What happens in chronic transplant rejection?
Both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)
What type of hypersensitivity is graft transplant rejection?
It is a type IV hypersensitivity reaction as there is a donor Tcell mediated attack against foreign recipient HLA (MHC)
o Suppression of the B cells, T helper cells, cytokines and complement in order to reduce chance of transplant rejection When after the transplant is the patient most heavily suppressed?
The patient is most heavily suppressed for the months after the transplant
Most patinets after a kidney transplant are on a triple therapy regime What does the triple therapy regime include?
A calcineurin inhibitor, a antimetabolite/blocks purine synthesis and prednisolone
What are the two options of calcineurin inhibtor that can be used in a renal transplant patinet?
Tacrolimus or ciclopsorin (CSA - ciclosporin A)
How do the two calcineurin inhibtors work?
They inhibit the activation of Thelper cells by cytochrome p450
What are the two calcineurin inhibitors, what is their mechanism and what are their side effects?
Ciclosporin and tacrolimus They inhibit the activation of Tcells by cytochrome p450 Side effects-Renal Dysfunction, Hypertension, Diabetes, Tremors
What are two antibmetabolites that work by blocing purine synthesis?
This is azathioprine and mycophenalate
What does the blocking of the purine synthesis cause?
Leads to suppression of proliferation of lymphocytes and B cells
What are the side effects of azathioprine and mycophenolate?
They can cause leucopaenia, anaemia and GI upset
Run through What are the two antibemtabolites? How do they work? What are there side effects?
Azathioprine and mycophenolate They work by blocking purine synthesis leading to increased suppression of lymphocytes and Bcells They can cause leucopaenia, anaemia and GI upset
What drug should azothioprine not be used in combination with and therefore mycophenolate would definitely be the antimetabolite chosen?
Do not used in combination with allopurinol - treatment of long term/recurrent gout
Steroids act non selectively to suppress activity of T cells and proliferation of B cells. Which steroid is used? Name some side effects of steroids?
Use prednisolone Osteoporosis Weight gain Diabetes and infection Easy bruising/thinning of the skin
There are 3 types of donor Name them
Deceased brain dead Deceased cardiac dead Living donor
